The underlying basis for the decline in ovarian function and the rise of serum in gonadotropins during menopause in humans is not known. The defect resulting in reproductive failure may reside in the ovary, exhaustion of primordial follicles; alteration of ovarian sensitivity to FSH and LH; or loss of sensitivity of the hypothalamo-hypophyseal axis to steriod feedback and LHRH. It would be difficult for moral reasons and length of time of postmenopause to study the aging hypothalamo-hypophyseal-ovarian axis in humans and for similar reasons and prohibitive costs to study it in subhuman primates. For these reasons the CBA strain of mice, an animal in which there is a drastic depletion of oocytes in aging, and the aged rat, where there is no clearcut exhaustion in primary follicles will be used in these experiments. Serum and pituitary FSH, LH and Prl levels will be determined in rats and mice 3 to 24 months of age. Changes in these parameters with age will be determined. These studies will be correlated with changes in number and appearance of ovarian follicles in these animals together with ultrastructure of pituitary and ovaries in these animals. The change in the sensitivity of the hypothalamus-pituitary to steriod hormone negative feedback will be determined in castrated groups of animals. In other experiments, LHRH will be administered to intact animals of different age groups and the effect determined by observing changes in gonadotropin levels. LHRH will also be administered to castrated animals and to estrogen and/or progesterone pretreated castrated animals. The effect of multiple injections of LHRH will also be studied in the above animals to determine the capacity of gonadotropes to secrete and subsequently resynthesize new hormones. Through these studies it should be determined whether the rat or CBA mouse will be a more suitable animal to be used for future experiments. Changes in the above parameters will be determined and compared in animals approaching reproductive senescence. Greater insights should be obtained in the knowledge of the aging hypothalamo-hypophyseal-ovarian axis.